Adjuvant nitrosourea chemotherapy fails to prolong survival significantly as many tumors demonstrate resistance to these drugs. It has been documented in cell lines that O6-methylguanine DNA methyltransferase (MGMT) plays an important role in chloroethylnitrosourea (CENU) drug resistance.

We evaluated MGMT expression in 22 glioma specimens by using an immunofluorescence assay and compared the results with clinical responses of the patients to CENU-based chemotherapy.

Eight tumor samples had no detectable MGMT, whereas other samples had from 9,989 to 982,401 molecules/nucleus. In one group (12 patients), the tumor decreased in size or was stable (effective group), whereas in the other group (10 patients), the tumor demonstrated continuous growth during chemotherapy (progressive group). The Mer- patients (MGMT < 60,000 molecules/nucleus) appeared to have more chance of stable disease or response to CENU therapy than the Mer+ patients (MGMT > 60,000 molecules/nucleus) (X2 = 4.791, p = 0.0286). In patients with glioblastomas multiforme (GBMs), the median time to progression (TTP) of Mer+ patient was shorter than that of Mer- patient (t = 2.04, p = 0.049). As a corollary, the MGMT levels were significantly higher in GBM tumors from the progressive group than those from the effective group (t = 2.26, p = 0.029). However, there was no significant correlation between MGMT levels and either the survival time (r = 0.04, p = 0.8595) or TTP (r = 0.107, p = 0.6444).

This study suggests that being MGMT positive is indicative of a more aggressive disease that progresses more rapidly with CENU therapy. However, MGMT negative tumors are not always sensitive to CENU agents, suggesting that other factors are also important.

To determine the etiology, early mortality, predictors of prognosis and diagnostic yields of EEG and CT scans of the head in new-onset seizures in elderly patients.

EEG records for the north-central region of Saskatchewan, between 01/94 and 12/95 were reviewed to identify all adults aged 60 years or older with new-onset seizures. Information on demographics, seizure type, etiology, EEG and neuroimaging studies, anti-epileptic treatment and course of epilepsy was obtained by review of medical records and interview with the patient and/or family member.

Of 88 eligible subjects, 61 (69%) were contacted for follow-up, 19 (22%) were deceased (12 of whom who had a serious underlying etiology to their seizures, which was obvious at the time of initial presentation and led shortly to their demise), 4 (5%) were lost to follow-up and 4 (5%) refused participation. Excluding those refusing participation, 74/84 (88%) patients presented with partial or secondarily generalized seizures. Seizures were cryptogenic in 38/84 (45%), and due to stroke in 19/84 (23%). EEGs were abnormal in 61/84 (73%) cases, with epileptiform discharge in 33/84 (39%). CT scans were abnormal in 57/84 (68%) cases with acute pathology in 29/84 (35%). Of the 61 patients participating in the follow-up interview, 54 (89%) were treated with anti-epileptic medication and seizure control was usually successful. Predictors for ongoing seizures were more than 3 seizures at presentation, epileptiform activity on initial EEG and discontinuation of anti-epileptic medication for lack of efficacy.

Prognosis of new-onset seizures in elderly patients is favorable if seizures are not symptomatic of a life-threatening disorder.

Access to multiple sclerosis (MS) diagnosis in Canada has never been assessed. This study was designed to examine the pattern of MS diagnosis in Canada, including neurologists' diagnostic approach and waiting times for investigations.

A mail survey was forwarded to every registered neurologist in Canada (n = 479) in late 1996. Questions included their diagnostic approach to MS including perceived waiting times for various investigations including MRI. Actual MRI waiting periods were separately obtained from booking clerks or neuroradiologists from every MRI unit in Canada.

153 responses were received. Neurological assessment is obtained, on average, 1 month after referral. MRI is routinely ordered by 92% of neurologists for suspected MS followed by evoked potentials (EP) (36%) and lumbar puncture (LP) (17%). The perceived waiting period for EP and LP is less than one month but 3 months for MRI. This is very similar to the actual waiting periods obtained from the MRI units surveyed (mean of 101 days). There is a trend for longer waiting periods as one moved east to west (Eastern provinces — mean of 62 days, Ontario — 95 days, Quebec — 102 days and 122 days in the Western provinces). Private MRI units have appeared in the Western provinces and have the shortest waiting periods (2 weeks maximum). The current MRI/million population ratio in Canada is 1.8, far below the ratios of other developed nations.

Canadian neurologists prefer MRI of the brain to confirm an MS diagnosis and desire greater access to it. Access to neurological assessment, EP and LP is probably adequate but the average wait for MRI of 3 months is relatively long. The perceived average waiting period for MRI is similar to the actual waiting times of 3 months, with the Western provinces of Canada having the longest waits. Canada continues to have one of the lowest MRI/population ratios in the developed world.

Botulism may involve the autonomic nervous system.

We assessed the autonomic function of 6 botulism patients with heart rate variations, sympathetic skin responses, and plasma norepinephrine.

Two weeks after onset, all the patients had absent sympathetic skin response in the palm and sole. Compared with controls, the heart rate variation of botulism patients was significantly decreased at rest (3.1 ± 1.2% vs. 20.9 ± 2.0%, p = 0.0018) and during deep breathing (4.3 ± 2.3% vs. 29.7 ± 2.6%, p = 0.0018). The botulism patients had significantly lower plasma norepinephrine levels (supine 29.2 ± 10.1 pg/ml vs. 257.5 ± 65.8 pg/ml, p = 0.0018; standing 40.3 ± 13.1 pg/ml vs. 498.5 ± 85.6 pg/ml, p = 0.0018). The heart rate variation and sympathetic skin response was greatly improved 6 months after onset.

Heart rate variation, absence of sympathetic skin response, and low plasma norepinephrine are all manifestations of autonomic dysfunction in botulism patients.

The majority of patients with diffuse Lewy body disease have cognitive or psychiatric manifestations as part of their initial presentation. A sizable minority present with parkinsonian features alone. Autonomic features may also occur, typically after the development of cognitive changes. We aim to demonstrate that diffuse Lewy body disease may rarely also present with parkinsonism accompanied by marked autonomic dysfunction in the absence of significant cognitive or psychiatric abnormalities.

Case report based on a retrospective chart review and neuropathological examination.

We report on a patient in whom a clinical diagnosis of multiple system atrophy was made based on a presentation of parkinsonism with prominent and early autonomic involvement. The former included postural tremor, rigidity and bradykinesia, while the latter consisted of repeated falls due to orthostasis and the subsequent development of urinary incontinence midway through the course of her illness. She was poorly tolerant of dopaminergic therapy due to accentuated orthostasis. Benefit from levodopa was limited and only evident when attempted withdrawal resulted in increased rigidity. There was no history of spontaneous or drug-induced hallucinations, delusions or fluctuating cognition, and in contrast to the prominence and progression of her parkinsonian and autonomic features over the first several years, cognitive impairment did not occur until the final stages of her illness, seven years after the onset of initial symptoms. Neuropathological examination revealed numerous Lewy bodies in both neocortical as well as subcortical structures consistent with a diagnosis of diffuse Lewy body disease. There was marked neuronal loss in the substantia nigra as well as the autonomic nuclei of the brainstem and spinal cord.

In addition to cognitive, psychiatric, and parkinsonian presentations, diffuse Lewy body disease may present with parkinsonism and prominent autonomic dysfunction, fulfilling proposed criteria for the striatonigral form of MSA.

To summarize the evidence for neurologic uses of immunoglobulin, intravenous (IGIV) in light of present-day clinical usage. This summary guided the development of practice recommendations for the effective and efficient use of IGIV in Neurology.

MEDLINE was searched to identify pertinent English-language review articles and original reports (n = 231) on the use of IGIV in neurology (excluding editorials, letters, and comments) published before March 1998. Evidence on alternative therapies was only included as compared to IGIV. The relevant original reports and review articles and older classic studies (n = 92) were synthesized into an information foundation. Extracted data included laboratory and clinical findings, objective measures, and clinical impressions. Clinical recommendations were based on evidence quality, graded by study design, clinical experiences of IGIV in Neurology Advisory Board members, and the conditions of IGIV use in therapy.

In neurology, many disorders are poorly understood, and the mechanisms behind beneficial regimens even less so. As a result, it is fairly common for best-practice decisions to rest on weaker evidence. The usefulness of IGIV in neurology can be described by a “combined score” based on evidence quality and strength of impact. Combined scores ranged from A+ (strongly recommended) to C (recommended as a last resort). The following clinical recommendations are made: IGIV is: strongly recommended for the treatment of Guillain-Barré syndrome (A+); favorably recommended for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy, dermatomyositis, and multifocal motor neuropathy (A); recommended as a second resort for the treatment of multiple scerosis and myasthenia gravis (B); and recommended as a last resort for the treatment of polymyositis, inclusion-body myositis, intractable epilepsies, and stiff-man syndrome (C).